Cancers in addition to coronary artery disease are the main cause of death in developed countries, and the proportion of cancers is increasing steadily year by year. Moreover, among cancers, lung cancer, prostate cancer, pancreatic cancer, breast cancer, colon cancer, and ovarian cancer are typical causes of cancer death. Particularly, prostate cancer is the fourth prevalent cancer spreading in males worldwide. The development of the cancer is observed in approximately 20% of males in Europe and the United States. Furthermore, prostate cancer accounts for approximately 3.5% of deceased patients due to cancers in Japan, and as a recent trend, the proportion is rapidly increasing.
In addition, surgical resection, radiation therapy, hormonal therapy, and chemotherapy are given as the main treatment methods against prostate cancer and the like. Nevertheless, the effects of these treatment methods are small for many people. Hence, an effective treatment method has not been established against cancers yet at present.
Under such circumstances, the use of an antibody as an anticancer agent has drawn attention recently. The importance is increasingly recognized as an approach in treating various disease conditions (of cancer types). For example, in a case of an antibody targeting a tumor-specific antigen, the administered antibody is assumed to accumulate at the tumor. Accordingly, attack on cancer cells by an immune system through a complement-dependent cytotoxicity (CDC) activity or an antibody-dependent cell-mediated cytotoxicity (ADCC) activity can be expected. Moreover, by binding a drug such as a radionuclide or cytotoxic substance to an antibody in advance, the bound drug can be efficiently delivered to the tumor site. Thereby, the amount of the drug reaching to other tissues can be reduced, and consequently a reduction in side effect can be expected. By administering an antibody having an agonistic activity in a case where a tumor-specific antigen has an activity to induce cell death, or by administering an antibody having a neutralizing activity in a case where a tumor-specific antigen is involved in cell growth and survival, termination or shrinkage of tumor growth can be expected from the accumulation of the tumor-specific antibody and the activity of the antibody. Because of such abilities, it is thought that an antibody is suitably applied as an anticancer agent.
As antibody drugs having been put on the market so far for leukemia and lymphoma, rituximab (product name: Rituxan) and inotuzumabozogamicin (product name: Zevailn) targeting CD20, gemtuzumab ozogamicin (product name: Mylotarg) targeting CD33, and so forth have been developed. Further, against epithelial solid cancer such as breast cancer, trastuzumab (product name: Herceptin) targeting Her2/neu, bevacizumab (product name: Avastin) targeting VEGF, and so forth have been developed.
However, the number of antibody drugs approved by 2008 is approximately 20 in the United States and approximately 10 in Japan. Particularly, against solid cancers, only few antibody drugs are effective. Hence, further development of effective antibody drugs is desired, and it is strongly desired to identify particularly target molecules (antigen, epitope) that greatly influence the effectiveness of antibody drugs.
Meanwhile, as a protein involved in infections by coxsackieviruses and the like, coxsackievirus and adenovirus receptor (CXADR) is known. In addition, regarding this protein, it has been reported that the expression is promoted in ovarian cancer and skin basal cell carcinoma (PTL 1). On the other hand, a homozygous deletion of CXADR has been observed in cholangiocarcinoma, suggesting that CXADR functions as a tumor suppressor gene (PTL 2).
Although there are reports about the association between CXADR and cancer as described above, whether CXADR contributes to the development, malignant transformation, and the like of a cancer, or functions in a suppressive manner is not confirmed at present. Thus, it is still unknown whether an antibody against CXADR can have an anti-cancer activity.